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Picornaviruses. Picornaviruses. Small ( pico ) RNA Naked capsid >230 members 5 genera. Picornaviruses. 5 genera Enterovirus Rhinovirus Heparnavirus Cardiovirus Aphtovirus. Picornaviruses. Enteroviruses At least 72 serotypes Polioviruses Coxsackieviruses Echoviruses.
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Picornaviruses • Small (pico) • RNA • Naked capsid • >230 members • 5 genera
Picornaviruses • 5 genera Enterovirus Rhinovirus Heparnavirus Cardiovirus Aphtovirus
Picornaviruses • Enteroviruses At least 72 serotypes • Polioviruses • Coxsackieviruses • Echoviruses
International Virus Taxonomi committee • Enterovirus genus (EV): Poliovirus and EV A, B, C and D. • Parechovirus cinsi (PeV): echovirus 22 ve 23
Picornaviruses • Enteroviruses (EV) At least 72 serotypes • Polioviruses • Coxsackieviruses • Echoviruses • Human parechoviruses 1-3 (HPeV)
Picornaviridae • Enterovirus • Poliovirus type 1, 2, and 3 • Coxsackie A virus types 1 to 22 and 24 • Coxsackie B virus types 1 to 6 • Echovirus (ECHO virus) types 1 to 9, 11 to 27, and 29 to 34 • Enterovirus 68 to 71 • Rhinovirus types 1 to 100+ • Cardiovirus • Aphtovirus • Heparnavirus • HAV
Picornaviruses • Enteroviruses • Capsid very resistant facilitates transmission by the fecal-oral route • Infection initiated in the gastrointestinal tract • “Rarely cause enteric disease” • Infections are usually asymptomatic
Picornaviruses • Enteroviruses • Coxsackieviruses Town of Coxsackie, NY first isolation • Groups A and B
Picornaviruses • Enteroviruses • Echoviruses enteric cytopathic human orphan 32 serotypes
Picornaviruses • Rhinoviruses • Major cause of common cold • Sensitive to acidic pH and replicate poorly @ temperatures above 33oC URT
Picornaviruses/Structure • + sense, ssRNA • 7400 b • Icosahedral capsid • 4 virion peptides: VP1-4 • Encodes a polyprotein, two proteases, and an RNA-dependent RNA polymerase
Picornaviruses/Replication • The specifity of the picornavirus interaction for cellular receptors is the major determinant of the target tissue tropism and disease • VP1 and “canyon” • 80% of rhinoviruses and several serotypes of of coxsackieviruses recognize ICAM-1 • polio a different molecule
http://www.mcb.uct.ac.za/tutorial/picorna.html • This is an image reconstruction from X-ray crystallographic data of the r16 common cold virus: this is a member of the Rhinovirus genus of the Picornaviridae. Click on picture, then on the ">>" of the AAPLAY control line to animate: this will display the inner and outer capsid structures. VP1 is blue and clustered around the twelve 5-fold rotational axes; VP2 and 3 are green and red respectively, and cluster around the twenty local 6-fold rotational axes. VP4 can only be seen internally, where it clusters around 5-fold axes
Enteroviruses/Pathogenesis&Immunity • The diseases produced by the enteroviruses are determined mainly by differences in tissue tropism and cytolytic capacity of the virus • Poliovirus with the narrowest tissue tropism recognize a receptor expressed on anterior horn cells of the spinal cord, dorsal root ganglia, motor neurons, skeletal muscle cells, and few other cells
Enteroviruses/Pathogenesis&Immunity • Portal of entry: • URT • Oropharynx • Intestinal tract • Most enteroviruses are cytolytic • Excp: HAV • Viral shedding • From oropharynx • From the intestine (> 30 days)
Enteroviruses/Pathogenesis&Immunity • “Antibody is the major protective immune response to the enteroviruses”
Enteroviruses/Epidemiology • “The enteroviruses are exclusively human pathogenes” • Spread by the fecal-oral route • Asymptomatic shedding can occur • Poor sanitation and crowded living conditions foster transmission of the viruses • Enterovirus epidemics sewage contamination of water supplies • Outbreaks in schools & day care centers (summer) • Spread via resp. tract coxsackie & echov.
Enteroviruses/Epidemiology • Poliovirus has been eliminated from the Western Hemisphere, but • “not from the world” • Polio cause more severe disease in late childhood, the adolescent years, or adulthood • Coxsackie A mor severe in adults than children • Coxsackie B & some echo“s” can be particularly harmful to infants
Enteroviruses/Clinical syndromes • Poliovirus infections • Asymptomatic illness (90%) • Abortive poliomyelitis (minor illness) • Nonspecific febrile illness (5%) • Nonparalytic poliomyelitis or aseptic meningitis • 1 to 2%, symptomes of the minor illness + CNS sm • Paralytic polio, the major illness • 0.1 to 2.0%
Enteroviruses/Clinical syndromes • Poliovirus infections • Paralytic poliomyelitis • Asymmetrical flaccid paralysis with no sensory loss • Poliovirus type 1 is responsible for 85% of cases • Vaccine-associated disease (reversion of type 2&3) • Recovery, within 6 months to 2 years • Bulbar poliomyelitis • More severe, 75% death, iron lungs (1950’s) • Postpolio syndrome (30-40 years later) in 20-80% of the original victims)
Enteroviruses/Clinical syndromes Coxsackievirus and echovirus infections • Herpangina • Several types of Coxsackie A • Hand-foot-and-mouth disease( a vesicular exanthem) • Usually caused by coxsackievirus A16 • Pleurodynia (Bornholm’s disease)(Devil’s grip) • Fever + unilateral low thoracic, pleuritic chest pain • Coxsackie B
Enteroviruses/Clinical syndromes Coxsackievirus and echovirus infections • Myocardial and pericardial infections • Coxsackie B • Occur sporadically in older children and adults • Most threatening in newborns • Febrile illness, sudden unexplained onset of heart failure high mortality
Enteroviruses/Clinical syndromes Coxsackievirus and echovirus infections • Viral (aseptic meningitis) • Acute febrile illness + CNS symptoms • Petechia or a rash • Summer and autumn outbreaks with Echo 11 • Fever, rash and common cold-like symptoms • Other diseases • Acute hemorrhagic conjunctivitis • Enterovirus 70 and coxsackie A24
Enteroviruses/Clinical syndromes Coxsackievirus and echovirus infections • Other diseases • Acute hemorrhagic conjunctivitis • Enterovirus 70 and coxsackie A24 • transplacental infection • Insulin-dependent diabetes • Coxsackie B
PeV • Respiratory infections • Gastrointestinal infections
Enteroviruses/Laboratory Diagnosis • Nükleic acit detection • Isolation • Serology: Antibody
Enteroviruses/Treatment • Pleconaril new antiviral drug
Enteroviruses/ Prevention & control “The prevention of paralytic polyomyelitis is one of the triumphs of modern medicine” Poliovirus vaccines: • IPV, developed by Jonas Salk • OPV, developed by Albert Sabin (live attenuated)
Rhinoviruses • Most important cause of the common cold and URTI • ICAM-1 • Unable to replicate in the GIT • Labile to “ pH” • Grow best @ 33oC • Infection can be initiated by as little as 1 (one) infectious viral particle • “Runny nose”
Rhinoviruses • Most important cause of URTI ~ 50% • Common cold: • Enteroviruses • Coronaviruses • Adenoviruses • Parainfluenza viruses
Rhinoviruses • Common cold symptoms • Sneezing • Rhinorrhea nasal obstruction • Mild sore throat • Headache • Malaise • Cough • Fever & rigors
Rhinoviruses • The clinical syndrome of the common cold is usually so characteristic that laboratory diagnosis is unnecessary!!